Efficacy and safety of trastuzumab deruxtecan in HER-2 expressing solid tumors: A systematic review and meta-analysis.

Abstract

e15021 Background: HER2 expressing solid tumors represent a diverse group of malignancies with expression of protein HER2, including mostly breast but also non-breast cancers such as gastric, lung, and colorectal cancers. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, has demonstrated clinical efficacy in breast cancer, but its role in other cancers expressing HER-2 remains less established. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-DXd in HER2 expressing solid tumors, focusing on cancers other than breast cancer. Methods: A comprehensive literature search was conducted in PubMed, Embase and Cochrane for studies evaluating T-DXd in HER2 expressing solid tumors. Data on objective response rate (ORR), complete response (CR), progression-free survival (PFS), overall survival (OS), were extracted. All analysis was done on Rstudio version 4.1.1 and forest plots were genrated using random effect model, and heterogeneity was assessed using I² statistics. Sensitivity analyses evaluated the robustness of pooled results. Results: The analysis included five studies evaluating the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-positive solid tumors. Pooled analysis of efficacy paramters demonstrated significant advantage of T-DXd over chemotherapy across response rates, including OR for ORR being 3.14 (95% CI: 1.35-7.31), for CRR 3.68 (95% CI: 2.02-6.72) and for PRR being 3.67 (95% CI: 2.60-5.20). Overall survival significantly favored T-DXd (MD = 5.4, 95% CI: 2.73-8.07). Pooled analysis of progression free survival favoured T-DXd but the findings were non significant (MD = 1.82, 95% CI: 0.78-4.26). Conclusions: T-DXd demonstrates superior efficacy compared to chemotherapy in HER2-positive solid tumors, particularly in NSCLC and gastric cancers, with manageable safety concerns. These findings highlight the potential of T-DXd as a therapeutic option in both breast and non-breast HER2 expressing cancers, warranting further large-scale randomized controlled trials.